Transplantation and tumor Flashcards by Giovanna Zampierollo

one person to the same person

autograft

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person to a genetically identical recipient

syngraft

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person to a genetically different recipient

allograft

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graft to a different species

xenograft

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minutes or hours

hyperacute rejection

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due to preformed ab in the recipient

hyperacute rejection

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10-14 days

acute rejection

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due mainly to cell mediated immunity but some injury is also antibody mediated

acute rejection

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months or years after the transplant

chronic rejection

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Due to ab, T-cell and NK cell attack on the graft

chronic rejection

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mechanism of acute allograft rejection,

direct contact between _____ and the graft

CD8+

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mechanism of acute allograft rejection,

inflammation, macrophage activation, infiltration of phagocytic cells

locally released cytokines and chemokines

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mechanism of acute allograft rejection, complement binding and ADCC (ab dependent cellular cytotocicity by NK cells

Ab against donor HLA

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mechanism of acute allograft rejection,

direct

NK cell attack

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Stem cells can be obtained from the _____________ (after treatment with colony stimulating factors) or from ____________ blood or from ____________.

Stem cells can be obtained from the peripheral blood (after treatment with colony stimulating factors) or from umbilical cord blood or from bone marrow.

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The major danger of bone marrow transplantation

competent T-cells from the donor may be transplantated giving rise to graft versus host disease

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a reaction of donor T-cells against recipient MHC

graft versus host disease

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For a GVH to occur: [3]

graft must contain live T-cells
recipient must be immunosuppressed
donor and recipient must have different HLA types

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CD4+ T cells in the graft are activated by allogeneic molecules and produce a ______________

“cytokine storm”

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cytokine storms recruits __________, ____________ and ____________ to create the severe inflammation characteristic of GVH

other T cells, macrophages and NK cells

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acute GVHD rash that characteristically involves

palms and soles

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when a kidney is transplanted the __________ T cells attack the transplant

recipient

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When the bone marrow is transplanted the T cells in the ________ attack the recipient tissues

transplant

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recipient T cells attack

transplant rejection

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T cells in the transplant attack

Graft versus host disease

block a T-cell phosphatase and inhibit cytokine production and that serves as a immunosuppressive Drugs

cyclosporine and FK506

calcineurin

T-cell phosphatase that inhibits cytokine production

inhibit cytokine production and are anti-inflammatory and that serves as a immunosuppressive Drugs

corticosteroids

monoclonal antibody that serves as a immunosuppressive Drugs

Anti-CD3

antibody that serves as a immunosuppressive Drugs

Anti-IL-2 receptor

no b-cell involvement

GVH

problem with all forms of immunosuppressive therapy

normal immune response sagainst microorganisms are reduced giving rise to an increased incidence of infection

candida

fungi

pox and herpes viruses

large viruses

mycobacterium tuberculosis

intracellular bacteria

toxoplasma

intracellular parasites

tumor express a variety of tumor antigens that can be recognized by the immune system

tumor immunology

types of antigens on the surface of tumor cells [5]

1. virally controlled antigens 2. oncofetal antigens 3. mutant antigens 4. abnormal peptides made by tumor cells 5. tissue specific differentiation antigens

primary hepatocellular carcinoma

alpha-fetoprotein

colon carcinoma

carcino-embryonic antigen

alpha-fetoprotein and CEA- carcino-embryonic antigen

oncofetal antigens

PSA (prostate-specific antigen), B-cell (CD19, CD20) and T-cell markers (CD3, CD4 or CD8)

Tissue specific differentiation antigens

Her2/neu

mutatn antigens

fetal liver

alpha-fetoprotein

Her2/neu found on breast cancer can be tx. with

Herceptin

PSA

prostate-specific antigen

all kappa or all lambda?

lymphoma

changes on the surface of malignant cells that can occurs?

tumors may lose HLA class 1

tumors that have lost HLA class I ____________ but thwy will be killed by

will not be killed by CD8+ cells and NK cells that recognize and are cytotoxic to HLA Class I negative cells

large granuloar lymphocytes and destroy infected and malignant cell that have absent or defective MHC I

NK cells

NK cells have __ receptors that can bind to ______ resulting in ADCC

NK cells have Fc receptors that can bind to IgG resulting in ADCC

NK cells can be activated by

cytokines" IL-2, IL-12 and IFN gamma

NK cells produce

variety of cytokines

Principal immune mechanism of killing tumor cells is by

cytotoxic CD28 cells

killing of tumor cells can also take place by

activated macrophages and by NK cells

How do tumors escape?

1) They release immunosuppressive factors e.g. IL-10 and TGF-beta 2) They release factors that activate TREG cells 3) They select antigen-negative variants 4) They upregulate the expression of immune checkpoint molecules such as PD-1 and PD ligand 1 (PD-L1)

cytotoxic CD8 cells kill by

using granzyme and perforin, and expression of FasL on the CD8 cell

Cancer immunotherapy [5]

1) Immunization against oncogenic viruses 2) Stimulation of innate immune mechanisms 3) Checkpoint inhibitors 4) CAR T-cells 5) Monoclonal antibodies

1) Immunization against oncogenic viruses

Hep B and HPV

Stimulation of innate immune mechanisms [2]

1. Imiquimod activates a Toll like receptor (TLR7) | 2. BCG produces inflammation in bladder wall

checkpoint inhibitors

block CTLA-4 or the PD-1/PDL-1 interaction to remove the “brakes” from cytotoxic T-cells

magic bullets –immunotoxins

monoclonal antibodies

risks of blocking CTLA-4 or PD-1:

autoimmune reactions

less severe autoimmune reactions is with an

anti-PD1 antibody

are monoclonal antibodies attached to toxins such as ricin or radioactive isotopes.

immunotoxins

These are delivered specifically to the malignant cells to initiate direct killing.

immunotoxins

targets CD20 on B-cell lymphomas

Rituximab

targets growth factor receptors in colon cancer

Erbitux

(anti Her2/Neu) blocks growth factor signaling

Herceptin

Mechanisms of MAb-mediated killing, [3]

1. complement-mediated lysis and phagocytosis 2. attach by macrophages or NK cells 3. signaling, leading to apoptosis or growth arrest

monoclonal Ab where one arm binds to CD3 and the other to CEA

bispecific T cell engagers

CEA-CD3

T-cell bispecific Ab

designed to redirect T cells to tumor cells by simultaneously binding to CD3 found on T cells and CEA, a tumor surface antigen

CEA-CD3 TCB

Transplantation and tumor Flashcards

exam 4 (73 cards)